A potent candicidal peptide designed based on an encrypted peptide from a proteinase inhibitor

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects Pub Date : 2024-02-13 DOI:10.1016/j.bbagen.2024.130583

Luís Henrique de Oliveira Almeida , Suellen Rodrigues Ramalho , Claudiane Vilharroel Almeida , Camila de Oliveira Gutierrez , Janaína de Cassia Orlandi Sardi , Antonio de Miranda , Ricardo Abreu de Oliveira , Samilla Beatriz de Rezende , Edson Crusca , Octávio Luiz Franco , Caio Fernando Ramalho de Oliveira , Marlon Henrique Cardoso , Maria Lígia Rodrigues Macedo

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引用次数: 0

Abstract

Antimicrobial peptides (AMP) represent an alternative in the treatment of fungal infections associated with countless deaths. Here, we report a new AMP, named KWI-19, which was designed based on a peptide encrypted in the sequence of an Inga laurina Kunitz-type inhibitor (ILTI). KWI-19 inhibited the growth of Candida species and acted as a fungicidal agent from 2.5 to 20 μmol L⁻¹, also showing synergistic activity with amphotericin B. Kinetic assays showed that KWI-19 killed Candida tropicalis cells within 60 min. We also report the membrane-associated mechanisms of action of KWI-19 and its interaction with ergosterol. KWI-19 was also characterized as a potent antibiofilm peptide, with activity against C. tropicalis. Finally, non-toxicity was reported against Galleria mellonella larvae, thus strengthening the interest in all the bioactivities mentioned above. This study extends our knowledge on how AMPs can be engineered from peptides encrypted in larger proteins and their potential as candicidal agents.

Abstract Image

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根据蛋白酶抑制剂的加密肽设计的强效杀螨肽。

抗菌肽（AMP）是治疗真菌感染的一种替代疗法，这种感染导致无数人死亡。在此，我们报告了一种名为 KWI-19 的新型 AMP，它是根据一种英格月桂树库尼茨型抑制剂（ILTI）序列中加密的肽设计而成的。KWI-19 可抑制白色念珠菌的生长，并在 2.5 至 20 μmol L-1 的范围内发挥杀菌作用，同时还与两性霉素 B 具有协同活性。动力学测定显示，KWI-19 可在 60 分钟内杀死热带念珠菌细胞。我们还报告了 KWI-19 的膜相关作用机制及其与麦角甾醇的相互作用。KWI-19 还被鉴定为一种有效的抗生物膜肽，对热带念珠菌具有活性。最后，据报道，KWI-19 还对 Galleria mellonella 幼虫无毒性，从而增强了人们对上述所有生物活性的兴趣。这项研究扩展了我们对如何从加密在较大蛋白质中的肽中设计出 AMPs 及其作为杀螨剂潜力的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. General subjects 生物-生化与分子生物学

CiteScore

6.40

自引率

0.00%

发文量

139

审稿时长

30 days

期刊介绍： BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.